BRPI0712899A2 - derivados de leptomicina - Google Patents

derivados de leptomicina Download PDF

Info

Publication number: BRPI0712899A2
Authority: BR; Brazil
Prior art keywords: oxo; derivative; ieptomycin; methyl; formula
Prior art date: 2006-06-09

Application number

BRPI0712899-1A

Other languages

English (en)

Portuguese (pt)

Inventor

Herve Bouchard

Alain Commercon

Ravi V J Chari

Original Assignee

Sanofi Aventis

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2006-06-09

Filing date

2007-05-23

Publication date

2013-01-08

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37311892&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BRPI0712899(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2007-05-23 Application filed by Sanofi Aventis filed Critical Sanofi Aventis

2013-01-08 Publication of BRPI0712899A2 publication Critical patent/BRPI0712899A2/pt

Links

YACHGFWEQXFSBS-RJXCBBHPSA-N leptomycin Chemical class OC(=O)/C=C(C)/C[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)/C=C(\C)/C=C/C[C@@H](C)\C=C(/CC)\C=C\[C@@H]1OC(=O)C=C[C@@H]1C YACHGFWEQXFSBS-RJXCBBHPSA-N 0.000 title claims abstract 6
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims abstract description 14
239000003153 chemical reaction reagent Substances 0.000 claims abstract description 12
239000011230 binding agent Substances 0.000 claims description 72
150000001875 compounds Chemical class 0.000 claims description 44
238000000034 method Methods 0.000 claims description 29
239000002253 acid Substances 0.000 claims description 26
239000003814 drug Substances 0.000 claims description 24
-1 2-mercaptoethyl Chemical group 0.000 claims description 23
206010028980 Neoplasm Diseases 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 20
201000011510 cancer Diseases 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 16
239000003446 ligand Substances 0.000 claims description 14
150000003573 thiols Chemical group 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
229930190887 Leptomycin Natural products 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
239000013078 crystal Substances 0.000 claims description 4
UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 4
150000004677 hydrates Chemical class 0.000 claims description 4
CYWGSFFHHMQKET-UHFFFAOYSA-N 2-methylsulfanylethanamine Chemical compound CSCCN CYWGSFFHHMQKET-UHFFFAOYSA-N 0.000 claims description 3
230000003287 optical effect Effects 0.000 claims description 3
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
QECBVZBMGUAZDL-JSADDXMJSA-N leptomycin A Chemical compound OC(=O)/C=C(C)/C[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)/C=C(\C)/C=C/C[C@@H](C)\C=C(/C)\C=C\[C@@H]1OC(=O)C=C[C@@H]1C QECBVZBMGUAZDL-JSADDXMJSA-N 0.000 claims description 2
BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 claims 1
IHVODYOQUSEYJJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)C(CC1)CCC1CN1C(=O)C=CC1=O IHVODYOQUSEYJJ-UHFFFAOYSA-N 0.000 claims 1
LCVDHXURABCEDA-UHFFFAOYSA-N 2-(methyldisulfanyl)ethanamine Chemical compound CSSCCN LCVDHXURABCEDA-UHFFFAOYSA-N 0.000 claims 1
101100476722 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SBA1 gene Proteins 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
208000021070 secondary pulmonary alveolar proteinosis Diseases 0.000 claims 1
230000001472 cytotoxic effect Effects 0.000 abstract description 14
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UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 abstract description 8
230000001225 therapeutic effect Effects 0.000 abstract description 5
210000004027 cell Anatomy 0.000 description 106
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
239000000562 conjugate Substances 0.000 description 45
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 24
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YACHGFWEQXFSBS-XYERBDPFSA-N leptomycin B Chemical class OC(=O)/C=C(C)/C[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)/C=C(\C)/C=C/C[C@@H](C)/C=C(/CC)\C=C\[C@@H]1OC(=O)C=C[C@@H]1C YACHGFWEQXFSBS-XYERBDPFSA-N 0.000 description 18
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
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YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
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NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
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ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
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MBPAUMHSIFBANF-UHFFFAOYSA-N 1-amino-2-methylpropane-2-thiol Chemical compound CC(C)(S)CN MBPAUMHSIFBANF-UHFFFAOYSA-N 0.000 description 3
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6863—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from stomach or intestines cancer cell
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Organic Chemistry (AREA)
Immunology (AREA)
Cell Biology (AREA)
Oncology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Saccharide Compounds (AREA)
Pyrane Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

BRPI0712899-1A 2006-06-09 2007-05-23 derivados de leptomicina BRPI0712899A2 (pt)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP06290948.6		2006-06-09
EP06290948A EP1864682A1 (en)	2006-06-09	2006-06-09	Leptomycin derivatives
PCT/IB2007/001328 WO2007144709A2 (en)	2006-06-09	2007-05-23	Leptomycin derivatives

Publications (1)

Publication Number	Publication Date
BRPI0712899A2 true BRPI0712899A2 (pt)	2013-01-08

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ID=37311892

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BRPI0712899-1A BRPI0712899A2 (pt)	2006-06-09	2007-05-23	derivados de leptomicina

Country Status (28)

Country	Link
US (2)	US7816543B2 (es)
EP (3)	EP1864682A1 (es)
JP (1)	JP5162581B2 (es)
KR (1)	KR20090018103A (es)
CN (2)	CN101466409B (es)
AR (1)	AR063668A1 (es)
AU (1)	AU2007258896B2 (es)
BR (1)	BRPI0712899A2 (es)
CA (1)	CA2654322A1 (es)
CL (1)	CL2007001648A1 (es)
CR (1)	CR10459A (es)
EA (1)	EA017345B1 (es)
EC (1)	ECSP088936A (es)
GT (1)	GT200800277A (es)
HN (1)	HN2008001788A (es)
IL (1)	IL195419A0 (es)
MA (1)	MA30689B1 (es)
ME (1)	MEP88208A (es)
MX (1)	MX2008015728A (es)
MY (1)	MY148231A (es)
NO (1)	NO20085127L (es)
NZ (1)	NZ572947A (es)
SG (2)	SG174067A1 (es)
TN (1)	TNSN08463A1 (es)
TW (1)	TWI411609B (es)
UA (1)	UA95959C2 (es)
WO (1)	WO2007144709A2 (es)
ZA (1)	ZA200810015B (es)

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EP1914242A1 (en)	2006-10-19	2008-04-23	Sanofi-Aventis	Novel anti-CD38 antibodies for the treatment of cancer
CN101732308B (zh) *	2008-11-17	2011-11-30	中国人民解放军军事医学科学院毒物药物研究所	来普霉素b的新用途及含有它的药物组合物和产品
CN102365021B (zh)	2009-02-05	2015-07-15	伊缪诺金公司	新型苯并二氮杂*衍生物
FR2947269B1 (fr)	2009-06-29	2013-01-18	Sanofi Aventis	Nouveaux composes anticancereux
FR2949469A1 (fr)	2009-08-25	2011-03-04	Sanofi Aventis	Derives anticancereux, leur preparation et leur application en therapeutique
AR078471A1 (es)	2009-10-02	2011-11-09	Sanofi Aventis	COMPUESTOS MAITANSINOIDES Y EL USO DE ESTOS PARA PREPARAR CONJUGADOS CON UN ANTICUERPO LOS CUALES SE UTILIZAN COMO AGENTES ANTICANCERIGENOS Y EL PROCEDIMIENTO DE PREPARACIoN DE ESTOS CONJUGADOS
TW201129384A (en)	2010-02-10	2011-09-01	Immunogen Inc	CD20 antibodies and uses thereof
FR2963007B1 (fr)	2010-07-26	2013-04-05	Sanofi Aventis	Derives anticancereux, leur preparation et leur application therapeutique
JP6049642B2 (ja)	2011-02-15	2016-12-21	イミュノジェン・インコーポレーテッド	複合体の調製方法
PL2872157T3 (pl)	2012-07-12	2020-07-13	Hangzhou Dac Biotech Co., Ltd	Koniugaty wiążących komórkę cząsteczek ze środkami cytotoksycznymi
GB201309807D0 (en) *	2013-05-31	2013-07-17	Pharma Mar Sau	Antibody drug conjugates
US20150148411A1 (en) *	2013-11-25	2015-05-28	The Rockefeller University	Compositions and methods for diagnosis and therapy of disorders related to alterations of myh9
CA2953371C (en) *	2014-06-30	2021-08-24	Tarveda Therapeutics, Inc.	Targeted conjugates and particles and formulations thereof
CA2996902C (en)	2015-10-02	2020-06-02	Genentech, Inc.	Pyrrolobenzodiazepine antibody drug conjugates and methods of use
JP7057278B2 (ja)	2015-10-28	2022-04-19	ターベダセラピューティクスインコーポレイテッド	Ｓｓｔｒ標的化コンジュゲート及び粒子並びにその製剤
TW201808336A (zh)	2016-05-11	2018-03-16	賽諾菲公司	用抗ｍｕｃ１類美登素免疫綴合物抗體治療腫瘤的治療方案
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HRP20231233T1 (hr)	2017-04-27	2024-01-19	Pharma Mar, S.A.	Antitumorski spojevi
WO2019030284A1 (en) *	2017-08-09	2019-02-14	Helmholtz-Zentrum für Infektionsforschung GmbH	NOVEL TARGETED CYTOTOXIC RATJADONE DERIVATIVES AND CONJUGATES THEREOF
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2006
- 2006-06-09 EP EP06290948A patent/EP1864682A1/en not_active Withdrawn
2007
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- 2007-05-23 CN CN2007800215355A patent/CN101466409B/zh not_active Expired - Fee Related
- 2007-05-23 EP EP07734635A patent/EP2032172B1/en active Active
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- 2007-05-23 BR BRPI0712899-1A patent/BRPI0712899A2/pt not_active IP Right Cessation
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- 2007-06-08 AR ARP070102511A patent/AR063668A1/es not_active Application Discontinuation
2008
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- 2008-11-24 US US12/276,568 patent/US7816543B2/en not_active Expired - Fee Related
- 2008-11-25 ZA ZA2008/10015A patent/ZA200810015B/en unknown
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- 2008-12-09 NO NO20085127A patent/NO20085127L/no not_active Application Discontinuation
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- 2008-12-26 MA MA31515A patent/MA30689B1/fr unknown
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Also Published As

Publication number	Publication date
JP2009539820A (ja)	2009-11-19
NO20085127L (no)	2009-01-08
US20090182038A1 (en)	2009-07-16
CN101466409B (zh)	2012-11-21
MEP88208A (en)	2011-12-20
EA200870615A1 (ru)	2009-04-28
US20110002947A1 (en)	2011-01-06
HK1134240A1 (en)	2010-04-23
EP2540320A1 (en)	2013-01-02
CN102731611A (zh)	2012-10-17
AR063668A1 (es)	2009-02-11
MX2008015728A (es)	2009-01-09
AU2007258896A1 (en)	2007-12-21
MA30689B1 (fr)	2009-09-01
ECSP088936A (es)	2009-01-30
MY148231A (en)	2013-03-29
UA95959C2 (en)	2011-09-26
ZA200810015B (en)	2010-02-24
TWI411609B (zh)	2013-10-11
EP1864682A1 (en)	2007-12-12
US7816543B2 (en)	2010-10-19
NZ572947A (en)	2011-12-22
GT200800277A (es)	2009-06-16
WO2007144709A3 (en)	2008-06-12
TW200812996A (en)	2008-03-16
CR10459A (es)	2009-01-09
SG174067A1 (en)	2011-09-29
HN2008001788A (es)	2012-08-27
IL195419A0 (en)	2009-08-03
EA017345B1 (ru)	2012-11-30
CN101466409A (zh)	2009-06-24
CA2654322A1 (en)	2007-12-21
EP2032172A2 (en)	2009-03-11
EP2032172B1 (en)	2012-06-06
AU2007258896B2 (en)	2013-01-24
CL2007001648A1 (es)	2008-01-18
TNSN08463A1 (en)	2010-04-14
SG174066A1 (en)	2011-09-29
WO2007144709A2 (en)	2007-12-21
JP5162581B2 (ja)	2013-03-13
KR20090018103A (ko)	2009-02-19

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2016-09-20	B08F	Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]	Free format text: REFERENTE A 9A ANUIDADE.
2017-01-10	B08K	Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette]	Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2385 DE 20-09-2016 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013.
2018-03-27	B15K	Others concerning applications: alteration of classification	Ipc: A61K 47/68 (2017.01), A61P 35/00 (2006.01)

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US8435528B2 (en)	2013-05-07	Cytotoxic agents comprising new maytansinoids
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